Probiotic-induced functional alterations in the gut microbiome of preterm infants

Preterm infants exhibit a distinct gut microbiomes characterized by a low microbial load and reduced microbial diversity. While probiotics have shown promise in transforming preterm infants’ microbiomes to resemble those of full-term infants, their influence on microbiome functionality remains underexplored. This study aimed to investigate the impact of probiotics on the functional development of the gut microbiota in pre-term infants. Our population study includes 105 preterm infants (gestational age 23-36 weeks) from the observation longitudinal BLOOM study, 68 of whom received a multi-strain probiotic treatment for the first eight weeks post-birth. We developed GEnome-scale Models (GEMs) of metabolism for each probiotic strain and species-resolved GEMs for the infants’ microbiota from 762 stool samples, incorporating known Human Milk Oligosaccharides (HMOs) degradation pathways. We simulated each GEM under a breastmilk diet. Species abundance analysis revealed that probiotics accelerated gut microbiota maturation in preterm infants. Metabolite profiling in feces using GEMs highlighted functional differences between control and probiotic groups, with notable increases in several metabolites in the latter. GEMs additionally pinpointed key microbial species and probiotic strains crucial for producing modulatory metabolites like short-chain fatty acids (SCFAs) and HMO degradants. Distinct microbial contributions to metabolite production were observed between the groups. Finally, shadow price analysis in GEMs indicated that the probiotic-treated microbiomes had enhanced capabilities for producing SCFAs and degrading HMOs, suggesting a more adaptable metabolic environment. Our study offers novel insights into how probiotics fundamentally shape the functional landscape and dynamics of pre-term infants’ gut microbiota development.